Genomic and immunohistochemical profiles of enteropathy-associated T-cell lymphoma in Japan

Sakura Tomita, Yara Y. Kikuti, Joaquim Carreras, Minoru Kojima, Kiyoshi Ando, Hirotaka Takasaki, Rika Sakai, Katsuyoshi Takata, Tadashi Yoshino, Silvia Bea, Elias Campo, Naoya Nakamura

Research output: Contribution to journalArticle

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Abstract

Enteropathy-associated T-cell lymphoma (EATL) is a rare primary T-cell lymphoma of the digestive tract. EATL is classified as either Type I, which is frequently associated with and thought to arise from celiac disease and is primarily observed in Northern Europe, and Type II, which occurs de novo and is distributed all over the world with predominance in Asia. The pathogenesis of EATL in Asia is unknown. We aimed to clarify the histological and genomic profiles of EATL in Japan in a homogeneous series of 20 cases. The cases were characterized by immunohistochemistry, high-resolution oligonucleotide microarray, and fluorescence in situ hybridization (FISH) at five different loci: 1q21.3 (CKS1B), 6q16.3 (HACE1), 7p22.3 (MAFK), 9q33.3 (PPP6C), and 9q34.3 (ASS1, CARD9) using formalin-fixed paraffin-embedded sections. The histological appearance of EATL ranged from medium-to large-sized cells in 13 cases (65%), small-to medium-sized cells in five cases (25%), and medium-sized in two cases (10%). The immunophenotype was CD2 + (60%), CD3ε+ (100%), CD4+ (10%), CD7+ (95%), CD8+ (80%), CD56+ (85%), TIA-1+ (100%), Granzyme B+ (25%), T-cell receptor (TCR)β+ (10%), TCRγ+ (35%), TCRγδ+ (50%), and double negative for TCR (six cases, 30%). All cases were EBER-. The genomic profile showed recurrent copy number gains of 1q32.3, 4p15.1, 5q34, 7q34, 8p11.23, 9q22.31, 9q33.2, 9q34.13, and 12p13.31, and losses of 7p14.1. FISH showed 15 patients (75%) with a gain of 9q34.3 with good correlation with array comparative genomic hybridization. EATL in Japan is characterized by non-monomorphic cells with a cytotoxic CD8+ CD56+ phenotype similar to EATL Type II. The genomic profile is comparable to EATL of Western countries, with more similarity to Type I (gain of 1q and 5q) rather than Type II (gain of 8q24, including MYC). The 9q34.3 gain was the most frequent change confirmed by FISH irrespective of the cell origin of αβ-T-cells and γδ-T-cells.

Original languageEnglish
Pages (from-to)1286-1296
Number of pages11
JournalModern Pathology
Volume28
Issue number10
DOIs
Publication statusPublished - Oct 3 2015

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Enteropathy-Associated T-Cell Lymphoma
Japan
T-Cell Antigen Receptor
Fluorescence In Situ Hybridization
T-Lymphocytes
Granzymes
Comparative Genomic Hybridization
T-Cell Lymphoma
Celiac Disease
Oligonucleotide Array Sequence Analysis
Paraffin
Formaldehyde
Gastrointestinal Tract
Immunohistochemistry

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Tomita, S., Kikuti, Y. Y., Carreras, J., Kojima, M., Ando, K., Takasaki, H., ... Nakamura, N. (2015). Genomic and immunohistochemical profiles of enteropathy-associated T-cell lymphoma in Japan. Modern Pathology, 28(10), 1286-1296. https://doi.org/10.1038/modpathol.2015.85

Genomic and immunohistochemical profiles of enteropathy-associated T-cell lymphoma in Japan. / Tomita, Sakura; Kikuti, Yara Y.; Carreras, Joaquim; Kojima, Minoru; Ando, Kiyoshi; Takasaki, Hirotaka; Sakai, Rika; Takata, Katsuyoshi; Yoshino, Tadashi; Bea, Silvia; Campo, Elias; Nakamura, Naoya.

In: Modern Pathology, Vol. 28, No. 10, 03.10.2015, p. 1286-1296.

Research output: Contribution to journalArticle

Tomita, S, Kikuti, YY, Carreras, J, Kojima, M, Ando, K, Takasaki, H, Sakai, R, Takata, K, Yoshino, T, Bea, S, Campo, E & Nakamura, N 2015, 'Genomic and immunohistochemical profiles of enteropathy-associated T-cell lymphoma in Japan', Modern Pathology, vol. 28, no. 10, pp. 1286-1296. https://doi.org/10.1038/modpathol.2015.85
Tomita S, Kikuti YY, Carreras J, Kojima M, Ando K, Takasaki H et al. Genomic and immunohistochemical profiles of enteropathy-associated T-cell lymphoma in Japan. Modern Pathology. 2015 Oct 3;28(10):1286-1296. https://doi.org/10.1038/modpathol.2015.85
Tomita, Sakura ; Kikuti, Yara Y. ; Carreras, Joaquim ; Kojima, Minoru ; Ando, Kiyoshi ; Takasaki, Hirotaka ; Sakai, Rika ; Takata, Katsuyoshi ; Yoshino, Tadashi ; Bea, Silvia ; Campo, Elias ; Nakamura, Naoya. / Genomic and immunohistochemical profiles of enteropathy-associated T-cell lymphoma in Japan. In: Modern Pathology. 2015 ; Vol. 28, No. 10. pp. 1286-1296.
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abstract = "Enteropathy-associated T-cell lymphoma (EATL) is a rare primary T-cell lymphoma of the digestive tract. EATL is classified as either Type I, which is frequently associated with and thought to arise from celiac disease and is primarily observed in Northern Europe, and Type II, which occurs de novo and is distributed all over the world with predominance in Asia. The pathogenesis of EATL in Asia is unknown. We aimed to clarify the histological and genomic profiles of EATL in Japan in a homogeneous series of 20 cases. The cases were characterized by immunohistochemistry, high-resolution oligonucleotide microarray, and fluorescence in situ hybridization (FISH) at five different loci: 1q21.3 (CKS1B), 6q16.3 (HACE1), 7p22.3 (MAFK), 9q33.3 (PPP6C), and 9q34.3 (ASS1, CARD9) using formalin-fixed paraffin-embedded sections. The histological appearance of EATL ranged from medium-to large-sized cells in 13 cases (65{\%}), small-to medium-sized cells in five cases (25{\%}), and medium-sized in two cases (10{\%}). The immunophenotype was CD2 + (60{\%}), CD3ε+ (100{\%}), CD4+ (10{\%}), CD7+ (95{\%}), CD8+ (80{\%}), CD56+ (85{\%}), TIA-1+ (100{\%}), Granzyme B+ (25{\%}), T-cell receptor (TCR)β+ (10{\%}), TCRγ+ (35{\%}), TCRγδ+ (50{\%}), and double negative for TCR (six cases, 30{\%}). All cases were EBER-. The genomic profile showed recurrent copy number gains of 1q32.3, 4p15.1, 5q34, 7q34, 8p11.23, 9q22.31, 9q33.2, 9q34.13, and 12p13.31, and losses of 7p14.1. FISH showed 15 patients (75{\%}) with a gain of 9q34.3 with good correlation with array comparative genomic hybridization. EATL in Japan is characterized by non-monomorphic cells with a cytotoxic CD8+ CD56+ phenotype similar to EATL Type II. The genomic profile is comparable to EATL of Western countries, with more similarity to Type I (gain of 1q and 5q) rather than Type II (gain of 8q24, including MYC). The 9q34.3 gain was the most frequent change confirmed by FISH irrespective of the cell origin of αβ-T-cells and γδ-T-cells.",
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AU - Ando, Kiyoshi

AU - Takasaki, Hirotaka

AU - Sakai, Rika

AU - Takata, Katsuyoshi

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AU - Bea, Silvia

AU - Campo, Elias

AU - Nakamura, Naoya

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N2 - Enteropathy-associated T-cell lymphoma (EATL) is a rare primary T-cell lymphoma of the digestive tract. EATL is classified as either Type I, which is frequently associated with and thought to arise from celiac disease and is primarily observed in Northern Europe, and Type II, which occurs de novo and is distributed all over the world with predominance in Asia. The pathogenesis of EATL in Asia is unknown. We aimed to clarify the histological and genomic profiles of EATL in Japan in a homogeneous series of 20 cases. The cases were characterized by immunohistochemistry, high-resolution oligonucleotide microarray, and fluorescence in situ hybridization (FISH) at five different loci: 1q21.3 (CKS1B), 6q16.3 (HACE1), 7p22.3 (MAFK), 9q33.3 (PPP6C), and 9q34.3 (ASS1, CARD9) using formalin-fixed paraffin-embedded sections. The histological appearance of EATL ranged from medium-to large-sized cells in 13 cases (65%), small-to medium-sized cells in five cases (25%), and medium-sized in two cases (10%). The immunophenotype was CD2 + (60%), CD3ε+ (100%), CD4+ (10%), CD7+ (95%), CD8+ (80%), CD56+ (85%), TIA-1+ (100%), Granzyme B+ (25%), T-cell receptor (TCR)β+ (10%), TCRγ+ (35%), TCRγδ+ (50%), and double negative for TCR (six cases, 30%). All cases were EBER-. The genomic profile showed recurrent copy number gains of 1q32.3, 4p15.1, 5q34, 7q34, 8p11.23, 9q22.31, 9q33.2, 9q34.13, and 12p13.31, and losses of 7p14.1. FISH showed 15 patients (75%) with a gain of 9q34.3 with good correlation with array comparative genomic hybridization. EATL in Japan is characterized by non-monomorphic cells with a cytotoxic CD8+ CD56+ phenotype similar to EATL Type II. The genomic profile is comparable to EATL of Western countries, with more similarity to Type I (gain of 1q and 5q) rather than Type II (gain of 8q24, including MYC). The 9q34.3 gain was the most frequent change confirmed by FISH irrespective of the cell origin of αβ-T-cells and γδ-T-cells.

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